Adenosine receptor modelling. A1/A2a selectivity

Three-dimensional models of the A1 and A2a adenosine receptors (AR) were constructed by means of a homology procedure, using bovine rhodopsin as a template. In order to validate the two models, a docking analysis of selective agonists was carried out. The study shows that A1/A2a selectivity is mainly influenced by the different ability of the two receptors to give lipophilic interactions, instead of giving different H bonds. The binding site cavity of the A1AR is smaller than that of the A2aAR, and for this reason, less bulky ligands like CPA are able to give close interactions with the A1AR, unlike larger ligands such as CGS-21680. The different dimensions of the binding site cavity could be due to the presence of three residues of proline, which cause a different rearrangement of the TM, thus modifying the side chain disposition inside the inter-helix channel.

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